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APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development

Henderson, S, Chakravarthy, A, Su, X, Boshoff, C, Fenton, TR (2014) APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development. Cell reports, 7 (6). pp. 1833-1841. ISSN 2211-1247. (doi:10.1016/j.celrep.2014.05.012) (KAR id:61507)

Abstract

APOBEC3B cytosine deaminase activity has recently emerged as a significant mutagenic factor in human cancer. APOBEC activity is induced in virally infected cells, and APOBEC signature mutations occur at high frequency in cervical cancers (CESC), over 99% of which are caused by human papillomavirus (HPV). We tested whether APOBEC-mediated mutagenesis is particularly important in HPV-associated tumors by comparing the exomes of HPV+ and HPV- head and neck squamous cell carcinomas (HNSCCs) sequenced by The Cancer Genome Atlas project. As expected, HPV- HNSCC displays a smoking-associated mutational signature, whereas our data suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBEC-mediated driver mutations. Finally, we provide evidence that APOBEC activity is responsible for the?generation of helical domain hot spot mutations in the PIK3CA gene across multiple cancers. Our?findings implicate APOBEC activity as a key driver?of PIK3CA mutagenesis and HPV-induced transformation.

Item Type: Article
DOI/Identification number: 10.1016/j.celrep.2014.05.012
Additional information: © 2014 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Tim Fenton
Date Deposited: 21 Apr 2017 13:22 UTC
Last Modified: 09 Dec 2022 03:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61507 (The current URI for this page, for reference purposes)

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